U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Respiratory infections, recurrent, and failure to thrive with or without diarrhea(RIFTD)

MedGen UID:
1824079
Concept ID:
C5774306
Disease or Syndrome
Synonym: RIFTD
 
Gene (location): AGR2 (7p21.1)
 
Monarch Initiative: MONDO:0859370
OMIM®: 620233

Definition

Recurrent respiratory infections and failure to thrive with or without diarrhea (RIFTD) is characterized by neonatal onset of chronic cough, episodic wheezing, recurrent lower respiratory tract infections, chronic diarrhea, and failure to thrive. Despite the resemblance to cystic fibrosis (CF; 219700), these patients have normal sweat chloride and pancreatic elastase tests (Bertoli-Avella et al., 2022). [from OMIM]

Clinical features

From HPO
Mitral valve prolapse
MedGen UID:
7671
Concept ID:
C0026267
Disease or Syndrome
One or both of the leaflets (cusps) of the mitral valve bulges back into the left atrium upon contraction of the left ventricle.
Tricuspid regurgitation
MedGen UID:
11911
Concept ID:
C0040961
Disease or Syndrome
Failure of the tricuspid valve to close sufficiently upon contraction of the right ventricle, causing blood to regurgitate (flow backward) into the right atrium.
Right atrial enlargement
MedGen UID:
677114
Concept ID:
C0748427
Disease or Syndrome
Increase in size of the right atrium.
Pulmonary arterial hypertension
MedGen UID:
425404
Concept ID:
C2973725
Disease or Syndrome
Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Abdominal distention
MedGen UID:
34
Concept ID:
C0000731
Finding
Distention of the abdomen.
Cholestasis
MedGen UID:
925
Concept ID:
C0008370
Disease or Syndrome
Impairment of bile flow due to obstruction in bile ducts.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Chronic diarrhea
MedGen UID:
96036
Concept ID:
C0401151
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Gastroesophageal reflux
MedGen UID:
1368658
Concept ID:
C4317146
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
Hemiparesis
MedGen UID:
6783
Concept ID:
C0018989
Finding
Loss of strength in the arm, leg, and sometimes face on one side of the body. Hemiplegia refers to a complete loss of strength, whereas hemiparesis refers to an incomplete loss of strength.
Lethargy
MedGen UID:
7310
Concept ID:
C0023380
Sign or Symptom
A state of disinterest, listlessness, and indifference, resulting in difficulty performing simple tasks or concentrating.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Atelectasis
MedGen UID:
13946
Concept ID:
C0004144
Pathologic Function
Collapse of part of a lung associated with absence of inflation (air) of that part.
Bronchiectasis
MedGen UID:
14234
Concept ID:
C0006267
Disease or Syndrome
Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.
Cough
MedGen UID:
41325
Concept ID:
C0010200
Sign or Symptom
A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation.
Chronic cough
MedGen UID:
507601
Concept ID:
C0010201
Sign or Symptom
A persistent cough, defined as a cough lasting longer than eight weeks in adults or longer than four weeks in children.
Dyspnea
MedGen UID:
3938
Concept ID:
C0013404
Sign or Symptom
Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale.
Pleural effusion
MedGen UID:
10805
Concept ID:
C0032227
Disease or Syndrome
The presence of an excessive amount of fluid in the pleural cavity.
Crackles
MedGen UID:
11118
Concept ID:
C0034642
Finding
Crackles are discontinuous, explosive, and nonmusical adventitious lung sounds normally heard in inspiration and sometimes during expiration. Crackles are usually classified as fine and coarse crackles based on their duration, loudness, pitch, timing in the respiratory cycle, and relationship to coughing and changing body position.
Wheezing
MedGen UID:
21917
Concept ID:
C0043144
Sign or Symptom
A high-pitched whistling sound associated with labored breathing.
Exertional dyspnea
MedGen UID:
68549
Concept ID:
C0231807
Sign or Symptom
Perceived difficulty to breathe that occurs with exercise or exertion and improves with rest.
Recurrent lower respiratory tract infections
MedGen UID:
756211
Concept ID:
C3163798
Disease or Syndrome
An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections.
Bronchial wall thickening
MedGen UID:
898505
Concept ID:
C4084859
Finding
Radiological appearance of increased density around the walls of a bronchus or large bronchiole. This feature is thought to be related to edema involving the bronchial wall as well as the peribronchial interstitial space. If the cross section of a bronchus is captured in a radiograph or computed tomography image, it is said to have the appearance of a donut because of the central lucency representing the airway of the bronchus surrounded by a circular region of increased density.
Abnormal pulmonary interstitial morphology
MedGen UID:
1788738
Concept ID:
C5441745
Anatomical Abnormality
Abnormality of the lung parenchyma extending to the pulmonary interstitium and leading to diffuse pulmonary fibrosis.
Ground-glass opacification
MedGen UID:
1779663
Concept ID:
C5539411
Finding
On chest radiographs, ground-glass opacity appears as an area of hazy increased lung opacity, usually extensive, within which margins of pulmonary vessels may be indistinct. On CT scans, it appears as hazy increased opacity of lung, with preservation of bronchial and vascular margins. It is caused by partial filling of airspaces, interstitial thickening (due to fluid, cells, and/or fibrosis), partial collapse of alveoli, increased capillary blood volume, or a combination of these, the common factor being the partial displacement of air. Ground-glass opacity is less opaque than consolidation, in which bronchovascular margins are obscured.
Asthma
MedGen UID:
2109
Concept ID:
C0004096
Disease or Syndrome
Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.
Leukocytosis
MedGen UID:
9736
Concept ID:
C0023518
Disease or Syndrome
An abnormal increase in the number of leukocytes in the blood.
Hilar lymph node enlargement
MedGen UID:
629708
Concept ID:
C0456973
Disease or Syndrome
Hilar lymphadenopathy is swelling or enlargement of lymph nodes localised in hila, wedge-shaped anatomical structures containing pulmonary vessels, major bronchi, nerves and lymph nodes. Hilar lymph nodes are not visible on chest X-ray if they are not enlarged. Hilar lymph node enlargement can be caused by benign and malignant conditions and can be symmetrical (bilateral) or asymmetrical (unilateral).
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
Elevated sweat chloride
MedGen UID:
347278
Concept ID:
C1856646
Finding
An increased concentration of chloride in the sweat.
Upslanted palpebral fissure
MedGen UID:
98390
Concept ID:
C0423109
Finding
The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age.
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
Thin upper lip vermilion
MedGen UID:
355352
Concept ID:
C1865017
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective).
Mediastinal lymphadenopathy
MedGen UID:
451062
Concept ID:
C0520743
Disease or Syndrome
Swelling of lymph nodes within the mediastinum, the central compartment of the thoracic cavities that contains the heart and the great vessels, the esophagus, and trachea and other structures including lymph nodes.

Professional guidelines

PubMed

Kelly CR, Fischer M, Allegretti JR, LaPlante K, Stewart DB, Limketkai BN, Stollman NH
Am J Gastroenterol 2021 Jun 1;116(6):1124-1147. doi: 10.14309/ajg.0000000000001278. PMID: 34003176
Lacy BE, Pimentel M, Brenner DM, Chey WD, Keefer LA, Long MD, Moshiree B
Am J Gastroenterol 2021 Jan 1;116(1):17-44. doi: 10.14309/ajg.0000000000001036. PMID: 33315591
Feld LG, Neuspiel DR, Foster BA, Leu MG, Garber MD, Austin K, Basu RK, Conway EE Jr, Fehr JJ, Hawkins C, Kaplan RL, Rowe EV, Waseem M, Moritz ML; SUBCOMMITTEE ON FLUID AND ELECTROLYTE THERAPY
Pediatrics 2018 Dec;142(6) doi: 10.1542/peds.2018-3083. PMID: 30478247

Recent clinical studies

Etiology

Savarino E, Zingone F, Barberio B, Marasco G, Akyuz F, Akpinar H, Barboi O, Bodini G, Bor S, Chiarioni G, Cristian G, Corsetti M, Di Sabatino A, Dimitriu AM, Drug V, Dumitrascu DL, Ford AC, Hauser G, Nakov R, Patel N, Pohl D, Sfarti C, Serra J, Simrén M, Suciu A, Tack J, Toruner M, Walters J, Cremon C, Barbara G
United European Gastroenterol J 2022 Jul;10(6):556-584. Epub 2022 Jun 13 doi: 10.1002/ueg2.12259. PMID: 35695704Free PMC Article
Kotloff KL
Curr Opin Pediatr 2022 Apr 1;34(2):147-155. doi: 10.1097/MOP.0000000000001107. PMID: 35165210
Goodman C, Keating G, Georgousopoulou E, Hespe C, Levett K
BMJ Open 2021 Aug 12;11(8):e043054. doi: 10.1136/bmjopen-2020-043054. PMID: 34385227Free PMC Article
Andreyev J, Ross P, Donnellan C, Lennan E, Leonard P, Waters C, Wedlake L, Bridgewater J, Glynne-Jones R, Allum W, Chau I, Wilson R, Ferry D
Lancet Oncol 2014 Sep;15(10):e447-60. doi: 10.1016/S1470-2045(14)70006-3. PMID: 25186048
Allen SJ, Martinez EG, Gregorio GV, Dans LF
Cochrane Database Syst Rev 2010 Nov 10;2010(11):CD003048. doi: 10.1002/14651858.CD003048.pub3. PMID: 21069673Free PMC Article

Diagnosis

Savarino E, Zingone F, Barberio B, Marasco G, Akyuz F, Akpinar H, Barboi O, Bodini G, Bor S, Chiarioni G, Cristian G, Corsetti M, Di Sabatino A, Dimitriu AM, Drug V, Dumitrascu DL, Ford AC, Hauser G, Nakov R, Patel N, Pohl D, Sfarti C, Serra J, Simrén M, Suciu A, Tack J, Toruner M, Walters J, Cremon C, Barbara G
United European Gastroenterol J 2022 Jul;10(6):556-584. Epub 2022 Jun 13 doi: 10.1002/ueg2.12259. PMID: 35695704Free PMC Article
Shankar S, Rosenbaum J
J Paediatr Child Health 2020 Jul;56(7):1029-1038. doi: 10.1111/jpc.14986. PMID: 32725734
Younis M, Rastogi R, Chugh A, Rastogi S, Aly H
Clin Perinatol 2020 Jun;47(2):301-321. Epub 2020 Mar 5 doi: 10.1016/j.clp.2020.02.007. PMID: 32439113
Mullish BH, Williams HR
Clin Med (Lond) 2018 Jun;18(3):237-241. doi: 10.7861/clinmedicine.18-3-237. PMID: 29858434Free PMC Article
Zollner-Schwetz I, Krause R
Clin Microbiol Infect 2015 Aug;21(8):744-9. Epub 2015 Mar 11 doi: 10.1016/j.cmi.2015.03.002. PMID: 25769427

Therapy

Liao W, Chen C, Wen T, Zhao Q
J Clin Gastroenterol 2021 Jul 1;55(6):469-480. doi: 10.1097/MCG.0000000000001464. PMID: 33234881Free PMC Article
Collinson S, Deans A, Padua-Zamora A, Gregorio GV, Li C, Dans LF, Allen SJ
Cochrane Database Syst Rev 2020 Dec 8;12(12):CD003048. doi: 10.1002/14651858.CD003048.pub4. PMID: 33295643Free PMC Article
Ianiro G, Rizzatti G, Plomer M, Lopetuso L, Scaldaferri F, Franceschi F, Cammarota G, Gasbarrini A
Nutrients 2018 Aug 12;10(8) doi: 10.3390/nu10081074. PMID: 30103531Free PMC Article
Kelly CR, Khoruts A, Staley C, Sadowsky MJ, Abd M, Alani M, Bakow B, Curran P, McKenney J, Tisch A, Reinert SE, Machan JT, Brandt LJ
Ann Intern Med 2016 Nov 1;165(9):609-616. Epub 2016 Aug 23 doi: 10.7326/M16-0271. PMID: 27547925Free PMC Article
Hempel S, Newberry SJ, Maher AR, Wang Z, Miles JN, Shanman R, Johnsen B, Shekelle PG
JAMA 2012 May 9;307(18):1959-69. doi: 10.1001/jama.2012.3507. PMID: 22570464

Prognosis

Goodman C, Keating G, Georgousopoulou E, Hespe C, Levett K
BMJ Open 2021 Aug 12;11(8):e043054. doi: 10.1136/bmjopen-2020-043054. PMID: 34385227Free PMC Article
GBD 2016 Diarrhoeal Disease Collaborators
Lancet Infect Dis 2018 Nov;18(11):1211-1228. Epub 2018 Sep 19 doi: 10.1016/S1473-3099(18)30362-1. PMID: 30243583Free PMC Article
Troeger C, Khalil IA, Rao PC, Cao S, Blacker BF, Ahmed T, Armah G, Bines JE, Brewer TG, Colombara DV, Kang G, Kirkpatrick BD, Kirkwood CD, Mwenda JM, Parashar UD, Petri WA Jr, Riddle MS, Steele AD, Thompson RL, Walson JL, Sanders JW, Mokdad AH, Murray CJL, Hay SI, Reiner RC Jr
JAMA Pediatr 2018 Oct 1;172(10):958-965. doi: 10.1001/jamapediatrics.2018.1960. PMID: 30105384Free PMC Article
Andreyev J, Ross P, Donnellan C, Lennan E, Leonard P, Waters C, Wedlake L, Bridgewater J, Glynne-Jones R, Allum W, Chau I, Wilson R, Ferry D
Lancet Oncol 2014 Sep;15(10):e447-60. doi: 10.1016/S1470-2045(14)70006-3. PMID: 25186048
Walker CLF, Rudan I, Liu L, Nair H, Theodoratou E, Bhutta ZA, O'Brien KL, Campbell H, Black RE
Lancet 2013 Apr 20;381(9875):1405-1416. Epub 2013 Apr 12 doi: 10.1016/S0140-6736(13)60222-6. PMID: 23582727Free PMC Article

Clinical prediction guides

Abdullahi T, Nitschke G, Sweijd N
PLoS One 2022;17(4):e0262008. Epub 2022 Apr 19 doi: 10.1371/journal.pone.0262008. PMID: 35439258Free PMC Article
Lόpez-Vélez R, Lebens M, Bundy L, Barriga J, Steffen R
Travel Med Infect Dis 2022 May-Jun;47:102293. Epub 2022 Mar 2 doi: 10.1016/j.tmaid.2022.102293. PMID: 35247581
GBD 2016 Diarrhoeal Disease Collaborators
Lancet Infect Dis 2018 Nov;18(11):1211-1228. Epub 2018 Sep 19 doi: 10.1016/S1473-3099(18)30362-1. PMID: 30243583Free PMC Article
Ayukekbong JA, Mesumbe HN, Oyero OG, Lindh M, Bergström T
J Gen Virol 2015 Aug;96(8):1983-1999. Epub 2015 May 22 doi: 10.1099/vir.0.000194. PMID: 26002299
Ericsson CD
Int J Antimicrob Agents 2003 Feb;21(2):116-24. doi: 10.1016/s0924-8579(02)00282-0. PMID: 12615374

Recent systematic reviews

Karagiannis T, Avgerinos I, Liakos A, Del Prato S, Matthews DR, Tsapas A, Bekiari E
Diabetologia 2022 Aug;65(8):1251-1261. Epub 2022 May 17 doi: 10.1007/s00125-022-05715-4. PMID: 35579691Free PMC Article
Goodman C, Keating G, Georgousopoulou E, Hespe C, Levett K
BMJ Open 2021 Aug 12;11(8):e043054. doi: 10.1136/bmjopen-2020-043054. PMID: 34385227Free PMC Article
Oliva V, Lippi M, Paci R, Del Fabro L, Delvecchio G, Brambilla P, De Ronchi D, Fanelli G, Serretti A
Prog Neuropsychopharmacol Biol Psychiatry 2021 Jul 13;109:110266. Epub 2021 Feb 5 doi: 10.1016/j.pnpbp.2021.110266. PMID: 33549697
Oka P, Parr H, Barberio B, Black CJ, Savarino EV, Ford AC
Lancet Gastroenterol Hepatol 2020 Oct;5(10):908-917. Epub 2020 Jul 20 doi: 10.1016/S2468-1253(20)30217-X. PMID: 32702295
Allen SJ, Martinez EG, Gregorio GV, Dans LF
Cochrane Database Syst Rev 2010 Nov 10;2010(11):CD003048. doi: 10.1002/14651858.CD003048.pub3. PMID: 21069673Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Consumer resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...